Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fibre formation.
Destabilization of nucleophosmin mRNA by the HuR/KSRP complex is required for muscle fibre formation.
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DOI：
10.1038/ncomms5190
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发表时间：
2014-06-27
影响因子：
16.6
通讯作者：
Gallouzi, Imed-Eddine
中科院分区：
文献类型：
--
作者：
Cammas, Anne;Sanchez, Brenda Janice;Lian, Xian Jin;Dormoy-Raclet, Virginie;van der Giessen, Kate;Lopez de Silanes, Isabel;Ma, Jennifer;Wilusz, Carol;Richardson, John;Gorospe, Myriam;Millevoi, Stefania;Giovarelli, Matteo;Gherzi, Roberto;Di Marco, Sergio;Gallouzi, Imed-Eddine
HuR通过在肌细胞融合形成肌管期间稳定MyoD、Myogenin和p21 mRNA来促进肌生成。在这里，我们表明，HuR，通过一种新的mRNA去稳定化活性，通过减少细胞周期启动子核磷蛋白（NPM）的表达，促进肌肉发生的早期步骤。HuR的缺失稳定NPM mRNA，增加NPM蛋白水平并抑制肌生成，而其过表达则产生相反的效果。NPM mRNA不稳定涉及HuR与衰变因子KSRP以及核糖核酸酶PARN和外泌体的缔合。HuR的C-末端介导HuR-KSRP复合物的形成，并且足以维持低水平的NPM mRNA以及促进肌细胞对肌生成的承诺。因此，我们提出了一个模型，其中下调NPM mRNA，介导的HuR，KSRP及其相关的核糖核酸酶，是必要的适当的肌生成。
HuR promotes myogenesis by stabilizing the MyoD, Myogenin and p21 mRNAs during the fusion of muscle cells to form myotubes. Here we show that HuR, via a novel mRNA destabilizing activity, promotes the early steps of myogenesis by reducing the expression of the cell cycle promoter nucleophosmin (NPM). Depletion of HuR stabilizes the NPM mRNA, increases NPM protein levels and inhibits myogenesis, while its overexpression elicits the opposite effects. NPM mRNA destabilization involves the association of HuR with the decay factor KSRP as well as the ribonuclease PARN and the exosome. The C-terminus of HuR mediates the formation of the HuR-KSRP complex and is sufficient for maintaining a low level of the NPM mRNA as well as promoting the commitment of muscle cells to myogenesis. We therefore propose a model whereby the downregulation of the NPM mRNA, mediated by HuR, KSRP and its associated ribonucleases, is required for proper myogenesis.
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影响因子：
4.5
作者：
Gallouzi, IE;Brennan, CM;Steitz, JA
通讯作者：
Steitz, JA
影响因子：
5.3
作者：
Dormoy-Raclet, Virginie;Menard, Isabelle;Gallouzi, Imed-Eddine
通讯作者：
Gallouzi, Imed-Eddine
影响因子：
4.4
作者：
Dergunova, NN;Bulycheva, TI;Malashenko, OS
通讯作者：
Malashenko, OS
影响因子：
4.8
作者：
Drury, Gillian L.;Di Marco, Sergio;Gallouzi, Imed-Eddine
通讯作者：
Gallouzi, Imed-Eddine
影响因子：
14.9
作者：
Barreau C;Paillard L;Osborne HB
通讯作者：
Osborne HB